1. Field of the Invention
The present invention relates to a nozzle device for washing the inside of a reaction vessel suitably used for measurement of biochemical reactions such as immune reactions.
2. Description of the Related Art
A micro quantity of a component (hereinafter referred to as an "analyte") is measured in many cases by utilizing a biochemical reaction in which a substance having affinity to the analyte to be measured is employed. One example is a recently developed immune measurement method which measures a micro quantity of a substance in a sample derived from a living body (such as blood, serum, and urea) by utilizing an immune reaction. In this method, the analyte is a component which appears or grows in a living body at the outbreak of a disease such as cancer, and the analyte is detected specifically by an antibody or an antigen. Another example employs a denatured portion of DNA, the main body of gene, as the analyte, in which the measurement is made by using a nucleic acid probe capable of hybridizing with the denatured portion. Any one of these methods includes a step of mixing a substance having affinity to the analyte with a sample containing the analyte, and a final step of measuring a labelled substance which is combined with the substance having affinity to the analyte.
The methods of measurement of the analyte by a biochemical reaction as mentioned above typically include a sandwich method and a competition method. These methods are explained below as specific examples of immune measurement. In the sandwich method, two antibodies (which may be a combination of an antibody with an antigen, or an antigen with an antibody) are mixed with an analyte to form an immune complex composed of three components. Into the one component other than the analyte, a labelling group (e.g., a fluorescent substance, a radioactive isotope, an enzyme, etc.) is introduced which is measurable directly or indirectly by optical means. Then the analyte is measured by an optical signal. On the other hand, in the competition method, a known amount of a preliminarily labelled analyte is added at the bonding reaction of the analyte with a substance having affinity thereto.
The methods explained above employ a labelled substance having affinity to the analyte, or a known quantity of a labelled analyte which has a label detectable directly or indirectly by an optical means. After the bonding reaction, the substance which has not bonded with the analyte needs to be eliminated. For this purpose, one of the substances having affinity to the analyte in the sandwich method, or the substance having the affinity in the competition method is immobilized onto a water-insoluble material (namely a carrier), and thereafter the non-immobilized components is removed. In the procedure, the accuracy is raised by supplying a washing-liquid containing a washing agent, simultaneously with drainage of the reaction liquid, or by other procedure.
The aforementioned step of removal of nonimmobilized components is required not to tend to remove from the biochemical reaction vessel the carrier immobilizing the analyte complex, and not to adversely affect the complex formed on the carrier. For example, Japanese patent application No. Sho 61-157607 describes a nozzle device having a porous filter at the tip portion. With use of this nozzle device, the carrier is pressed by the porous filter at the tip portion, the liquid (reaction liquid) in the vessel is discharged, and a washing liquid is simultaneously supplied to dilute and discharge a remaining component through a discharge-and-feed tube placed at the center of the filter.
The inventors of the present invention conducted an experiment of repeatedly removing a reaction liquid in a reaction vessel with a nozzle device provided with a porous filter. In this experiment, after repetition of about 2000 times of the removal operation, the filter became clogged and the efficiency of reaction liquid removal became lowered. This was presumed to be caused by adherence, to the porous filter, of the substance to be removed such as a labelled substance not having been bonded to the analyte, a substance coming from the sample other than the analyte, or a stabilizer added to improve the efficiency of the biochemical reaction.